D-penicillamine and D-penicillamine-protein disulphide in plasma and synovial fluid of patients with rheumatoid arthritis.
1. The plasma pharmacokinetics of D-penicillamine (D-pen) and D-penicillamine-albumin disulphide (D-pen-alb) were examined over a dosage interval in six patients with rheumatoid arthritis. In two of these, 24 h synovial fluid profiles of D-pen and D-pen-alb were also obtained. 2. D-pen was undetectable in plasma at the beginning of the study. The peak concentration (5.4 +/- 1.2 microM) occurred at between 45 min and 2 h and the mean elimination half-life was 0.6 h. D-pen-alb, however, was present at a mean plasma concentration of 19.1 microM prior to dosage, peaked at 26.2 microM and was eliminated with a half-life of 40 h. 3. D-pen concentrations in synovial fluid rose more slowly and peaked lower than in plasma. D-pen-alb was present in synovial fluid of the patients at 50.1% and 83.6%, respectively, of the simultaneous plasma concentration prior to dosage. Concentrations varied during the study interval, corresponding to changes in plasma concentrations. 4. These results demonstrate that D-pen forms stable conjugates with protein in treated patients. The presence of D-pen-alb in relatively high concentrations throughout the dosage interval contrasts with the low concentrations and rapid elimination of D-pen. Both D-pen and D-pen-alb were also shown to be present at the putative site of drug action (the inflamed synovial joint) in concentrations lower than those in plasma.
Joyce
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Department of Clinical Pharmacology and Toxicology, St. Vincent's Hospital, University of New South Wales, Darlinghurst, Australia.
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D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004563:Electrochemistry; D006801:Humans; D008875:Middle Aged; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics*; D011485:Protein Binding; D012709:Serum Albumin / Q000493:pharmacokinetics*; D000075462:Serum Albumin, Human; D013582:Synovial Fluid / Q000378:metabolism*
D012709:Serum Albumin; C067695:penicillamine-albumin disulfide; D010396:Penicillamine; D000075462:Serum Albumin, Human